title: Synthesis, biological evaluation and molecular modeling of novel triazole-containing berberine derivatives as acetylcholinesterase and β-amyloid aggregation inhibitors.
abstract: A series of novel triazole-containing berberine derivatives were synthesized via the azide-alkyne cycloaddition reaction. Their biological activity as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. Among them, compound 16d, which featured a diisopropylamino substitution at the 4-position of triazole ring, was found to be a potent inhibitor of AChE, with IC(50) value of 0.044 μM. Compound 18d, which beares a butyl at the 4-position of the triazole ring, showed the highest potency of β-amyloid aggregation inhibition (77.9% at 20 μM). Molecular modeling studies indicated that the triazole moiety of berberine derivatives displayed a face-to-face π-π stacking interaction in a 'sandwich' form with the Trp84 (4.09 Å) and Phe330 (4.33 Å) in catalytic sites of AChE.
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Processing, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Shi
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Xingshu
authors.initials: X
authors.lastname: Li
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D010446:Peptide Fragments; D014230:Triazoles; C075222:amyloid beta-protein (1-42); D001599:Berberine; D000110:Acetylcholinesterase